The proposed studies are part of a research program on the anatomic organization of the prefrontal cortex, an integrative center for cognitive, mnemonic and emotional processes. The specific purpose of the proposed studies is to investigate the connection of basal and medial prefrontal cortices, which are major targets of the phylogenetically older limbic system on one hand, and more recently evolved neocortices, on the other. The use of a primate, the rhesus monkey, is predicated on the unique connections observed between the limbic system and the evolving neocortex in this species. A study of the largely unexplored basal and medial prefrontal cortices will offer a unique opportunity to determine the interaction of several sensory and motor systems with the limbic input in cortices associated with higher-order processes. Our previous studies indicate that the degree of limbic influence is associated with the anatomic pattern of communication between brain regions. This hypothesis will be tested further by investigating the sources of cortical and subcortical projections to the most primitive basal and medial limbic prefrontal cortices, and comparing these findings with input reaching more differentiated neighboring cortices. The proposed studies will be conducted in the context of principles that seem to be fundamental to the organization of the cortex, including consideration of the regional, laminar, and columnar distribution of cortical projections and neural markers. Connections will be studied using both horseradish peroxidase and fluorescent dyes to label the neurons of origin. A study of the least differentiated prefrontal cortices will provide information on the first linkage of limbic structures with the evolving neocortex and offer clues on the development of the cortex in phylogeny. These studies may have important implications for understanding the mechanisms underlying deficits in neurologic disorders including epilepsy and Alzheimer's disease in which the limbic system, in general, and the prefrontal cortex, in particular, are affected.